Enzyme compositions with reduced viral and microbial contamination

Abstract

The present invention pertains to an enzyme preparation obtained from e-beam irradiated animal tissue, such as porcine pancreas. The present invention also pertains to methods for making such enzyme preparations, pharmaceutical compositions comprising such enzymes preparations, and methods for using such pharmaceutical compositions and enzyme preparations.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 15 / 470,386, filed Mar. 27, 2017, which claims priority to U.S. Provisional Application No. 62 / 314,048, filed Mar. 28, 2016, U.S. Provisional Application No. 62 / 452,746, filed Jan. 31, 2017, and U.S. Provisional Application No. 62 / 454,184, filed Feb. 3, 2017, the entire contents of which are incorporated herein by reference.TECHNICAL FIELD[0002]The present invention relates to enzyme preparations derived from animal tissue, pharmaceutical compositions comprising such enzyme preparations, and methods for reducing the risk of viral and microbial contamination in such preparations and compositions. Exemplary enzyme compositions include pancreatic extracts suitable for therapeutic use, such as for the treatment and / or prophylaxis of maldigestion, and in particular maldigestion based on chronic exocrine pancreatic insufficiency, in mammals and humans.BACKGROUND[0003]Products...

AI Technical Summary

Benefits of technology

[0020]Another aspect of the present invention pertains to a method for producing an enzyme preparation derived from an animal tissue, wherein the enzyme preparation has a reduced viral and / or microbial contamination relative to the source animal tissue. The method includes a treatment sufficient to produce at least a three log10, preferably at least a four log10, reduction in viral and / or microbial contaminants compared to the source animal tissue. In certain embodiments, the treatment comprises subjecting intact source animal tissue to radiation, preferably electron beam radiation, to produce irradiated animal tissue. In certain embodiments, the electron beam radiation treatment is sufficient to reduce viral and / or microbial contamination of the source animal tissue, while maintaining at least one biological activity of the source animal tissue. In certain embodiments, the biological activity is lipase activity. In certain embodiments, one or more enzymes and / or proenzymes are extracted from the irradiated animal tissue. In certain embodiments, one or more enzymes are isolated from the irradiated animal tissue. In certain embodiments, the method reduces the risk of infectious contamination of the animal-derived enzyme preparation or a pharmaceutical composition comprising the animal-derived enzyme preparation relative to an untreated control.

Problems solved by technology

Products derived from animal tissue may exhibit viral and / or microbial contamination.

A particular challenge is the inactivation or removal of viruses from enzyme compositions derived from animal tissue without destroying or changing the activity of the enzymes in the process.

However, many non-enveloped viruses are generally not inactivated by solvent or detergent treatment.

While dry heat treatment may inactivate even highly resistant viruses, such as non-enveloped viruses, the treatment requires extended time periods (of several hours) and monitoring of moisture content.

Moreover, heat treatment can compromise the desired biological activity of the product, particularly where the product is an enzyme composition.

However, there is relatively little lipase from sources other than the pancreas involved in digestion of lipids.

Thus, patients with untreated exocrine pancreatic insufficiency typically have difficulty digesting fat and may suffer symptoms of maldigestion or malnutrition or both, with deficiencies of essential fatty acids and fat-soluble vitamins, weight loss, cramping, flatulence, bloating, and greasy, foul-smelling, loose stools (steatorrhea).

For patients with CF, inadequate treatment may have serious consequences, as good nutritional status has been directly correlated with good lung function.

The pancreatic digestive enzymes are not secreted into the intestine, and thereby digestion of starch, fat, and protein is impaired.

The lack of digestion results in steatorrhea, abdominal pain, and weight loss, among others.

The consequences of the deficiency of digestive enzymes may be severe symptoms of under-nutrition and malnutrition, which may be accompanied by increased susceptibility to secondary illnesses.

Governmental regulations often require that pancreas glands be obtained from a single species slaughterhouse (i.e., no other species are slaughtered and processed at that facility) and, thereby limit the availability of starting material.

Wide-spread contamination of facilities with infectious agents may lead to a shutdown of production and to supply shortfall.

Current testing procedures may identify contaminated lots and elimination of such lots place further burdens on an already constrained supply of starting material.

In addition, PPV is a common model virus as it is difficult to inactivate by standard methods, such as chemical or thermal processing.

Thus, process steps that can be effective against difficult-to-inactivate viruses, such as PPV, have a high potential for changing the nature of the pancreatin product by degrading or reducing the pancreatic enzymes, particularly lipase, to unacceptable levels.

Such changes in potency may reduce or alter the efficacy profile of the ultimate product.

In particular, there was skepticism in the industry that a suitable robust, orthogonal viral clearance step could be developed without adversely impacting the chemical, physical, or pharmaceutical properties of pancreatin.